Portable, self-contained system for analyzing biological fluids or the like

ABSTRACT

A completely portable, self-powered system for rapidly and accurately measuring whole blood hematocrit and pH and levels of sodium, potassium, chloride and the other ions in blood and other fluids. The system includes a compact carrying case which contains an aluminum heat block with a glass electrode chamber therein. Individual selective ion electrodes are fitted in the electrode chamber. A reference electrode, a high-impedance electrode switch, a high-impedance solid-state electrometer, a direct readout scale calibrated in pH units and in milliequivalents per liter, and an integral rechargeable power supply are all contained in the carrying case. A heat control unit and a miniature centrifuge along with blood collecting accessories are included in the self-contained system for analyzing biological fluids.

United States Patent Stansell et al.

[ 51 Mar. 7, 1972 [54] PORTABLE, SELF-CONTAINED SYSTEM FOR ANALYZING BIOLOGICAL FLUIDS OR THE LIKE [72] lnventors: Marion .1. Stansell; Shelby J. Stansell, both of USAF Academy, C010.

[73] Assignees The United States of America as represented by the Secretary of the Air Force, by said Marion J. Stansell [22] Filed: Mar. 11, 1970 [21] Appl. No.: 18,574

[52] US. Cl. ..324/30 R, 23/230 B, 73/61 [51] Int. Cl. ..G0ln 27/42 [58] Field of Search ..324/29, 30; 73/61, 61.4;

230/230 B, 253 R, 259; 204/195 B, l T- [56] References Cited UNITED STATES PATENTS 2,886,771 5/1959 Vincent ..324/30 3,267,364 8/1966 Page ..324/30 3,148,146 9/1964 Asnes ...73/6l.4 3,556,950 1/1971 Dahms ..324/29 Primary Examiner--Michael .l. Lynch Attorney-Harry A. Herbert, Jr. and Arsen Tashjian 57 ABSTRACT A completely portable, self-powered system for rapidly and accurately measuring whole blood hematocrit and pH and levels of sodium, potassium, chloride and the other ions in blood and other fluids. The system includes a compact carrying case which contains an aluminum heat block with a glass electrode chamber thereinv Individual selective ion electrodes are fitted in the electrode chamber. A reference electrode, a high-impedance electrode switch, a high-impedance solid state electrometer, a direct readout scale calibrated in pH units and in milliequivalents per liter, and an integral rechargeable power supply are all contained in the carrying case. A heat control unit and a miniature centrifuge along with I blood collecting accessories are included in the self-contained system for analyzing biological fluids.

4 Claims, 5 Drawing Figures N/ 041: C: L LS JAM/.05 Came/run Patented March 7, 1972 3 Sheets-$heet 1 INVENTORS 14mm) J- .92'4 M54744 PORTABLE, SELF-CONTAINED SYSTEM FOR ANALYZING BIOLOGICAL FLUIDS OR THE LIKE BACKGROUND. OF TH E INVENTION This invention relates to a portableself-contained system for rapidly and reliably analyzingbiological fluids and, more particularly, the invention is concerned with providing a completely portable and self-powered unit with all accessories contained therein formaking multiple ion measurements on a single small blood sample and including centrifuge and temperature control capabilities.

Blood consists of plasma and cells floating within. Plasma is the residual material left after removing the cellular elements from the blood. By far the major constituents of plasma are proteins. In addition to the proteins there are many other important classes of compounds that circulate in the blood plasma. Most of these are smaller molecules which are freely diffusible through the capillaries and, in terms of concentra tion, the electrolytes are of most importance.

The electrolytes have a complex role in maintaining the physiological balance of the body. They maintain the normal neutral pH (7.3-7.5) of the blood by neutralizing the acidity of waste materials, control the water balance and participate in metabolic functions and blood coagulation. Slight deviations in pH may cause illness and marked deviations may cause death.

The important electrolytes commonly assayed in the blood are the anions, mainly chloride and bicarbonate, and the cations, mainly sodium with smaller concentrations of potassium, magnesium and calcium. Potassium, although present in low concentrations, is of considerable importance. Excessive or decreased potassium leads to various disorders chiefly involving the muscles, including the heart.

From the foregoing, it can be seen that the biochemical composition of blood plasma is often characteristically altered due to trauma or disease. Under ideal conditions the physician will subject the blood to frequent analysis for the purpose of determining the values of the chemical constituents of importance. This procedure generally requires that the blood be sent to a laboratory where cumbersome, complex and potentially dangerous, that is flammable gases, equipment is used to make the required determinations. This equipment is not readilyamenable to portability and ordinarily a relatively large volume of blood is required to make the tests by normal laboratory procedures. In emergency field hospitals, in medical staging operations, and during aeromedical evacuation, it is presently not feasible to carry out the hematologic procedures for making certain important determinations, particularly the patients electrolyte status and blood hematocrit. The delay in time, because of transportation and lack of facili ties, can be an important factor in the success or failure in the treatment and recovery of the injured or diseased patient.

SUMMARY OF THE INVENTION The present invention provides a system for making rapid and reliable measurements of blood hematocrit, blood pH, blood sodium, blood potassium, and blood chloride during aeromedical evacuation, in medical staging operations, in emergency field hospitals or on hospital wards at the patients bedside. The system is completely portable and self-powered with all accessories contained in the unit. Multiple ion measurements are made on a single small sample and a direct readout of pH, sodium, potassium and chloride is obtained. The power supply for the system includes rechargeable batteries with an integral battery charger operable from either 60 Hz. or 400 Hz. energy sources. An improved safety factor is obtained by eliminating the need of explosive gases as required in flame photometry and the closed sample system minimizes error due to gas exchange, etc. Operating instructions are read out by timer-indicator. A single combined standard and diluting fluid for assay of sodium, potassium and chloride is provided and a built-in capability for standardization before each unknown reading further simplifies the operation.

LII

Other features include a self-contained centrifuge and all solid-state electronics with a capability for recalibrating if necessary to replace electrodes. The temperature is controlled at 37 C. which permits readings that closely approach in vivo readings. Also, the analytic capability can be expanded by substituting appropriate electrodes and the system will assay any fluid if appropriate standards are used.

Accordingly, it is an object of the present invention to provide a portable, self-contained, battery operated system-for measuring whole blood hematocrit and levels of hydrogen ion, sodium ion, potassium ion, chloride ion and other ions in blood and other fluids.

Another object of the invention is to provide a unitized system for obtaining rapid and reliable measurement of blood hematocrit, blood pH, and other important analyses under emergency conditions outside the laboratory.

Still another object of the invention is to provide a system for making blood hematocrit and multiple ion measurements on a single small sample making the invention particularly valuable for use in pediatric services.

A further object of the invention is to provide a portable blood analyzing system wherein errors due to gas exchange or inadequate temperature control are kept to a minimum.

Another further object of the invention is to provide a blood hematocrit and electrolyte assaying system wherein the measuring means includes solid-state electronics for long term reliability and minimum battery drain.

A still further object of the invention is to provide a compact, self-contained, battery operated system for measuring blood hematocrit and multiple ion concentrations wherein the portability of the system will render it useful in the laboratory module of air transportable hospitals.

These and other objects, features and advantages will become more apparent after considering the description that follows taken in conjunction with the attached drawings wherein like numbers are used throughout to identify like elements.

DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagrammatic view of a complete analytic system according to the invention enclosed in a case showing the position of the various elements;

FIG. 2 is a functional diagram of the analytic system showing the flow pattern of the sample being analyzed;

FIG. 3 is an outline diagram of a rear view of the panel assembly showing the electronic and the fluid flow components;

FIG. 4 is an alternative embodiment of the electrode assembly in longitudinal cross section and features glass capillary electrodes; and

FIG. 5 is a cross-sectional view along the line 55 of FIG. 4.

DESCRIPTION OF A PREFERRED EMBODIMENT Referring now to the drawings, there is shown a portable, self-contained, battery operated system for measuring whole blood hematocrit and levels of hydrogen ion, sodium ion, potassium ion, chloride ion and other ions in blood and other fluids. In FIG. 1, which is an outline diagram of the system assembly in its carrying case 13, shows the relative positions of the various components. Rubber bumper strips 15 are attached to the outer surface of the case 13 for the purpose of providing impact protection and insulation from the effects of untoward vibrations. A momentary contact, single pole-single throw, pushbutton switch 17 for energyzing auxiliary heating circuits is positioned on the panel for use if rapid heating to 37 C. is desired. Spring loaded bayonet fasteners 19 are provided for attaching the panel to the case 13. A quick onequarter turn enables the panel assembly to be disengaged from the case 13.

A cylindrical rubber bumper 21 is positioned in the space 23 and makes finn contact with the miniature centrifuge 25 when the case 13 is in the closed position. This bumper 21 prevents the centrifuge 25 from moving from its charger base 27 during transit. A load control knob 29 operates two syringes located behind the panel. The clockwise motion of the knob 29 simultaneously withdraws the syringe plungers from the barrels and the counterclockwise motion empties the contents of the syringes into a waste receptacle. A loop of Tygon tubing 31 extends through the panel and permits visual observation of the whole blood as it moves through various sections of the system. The flow valve knob 33 determines the flow of blood either to the test apparatus or to the waste receptacle.

An inlet jack 35 is positioned on the panel for a cable which connects to either 115 V. AC 60 Hz. or 400 Hz. Behind the panel, the jack 35 connects to a solid-state charger circuit which recharges the nickel-cadmium batteries during storage. The cable 37 leads from the solid-state charger circuits (behind panel) to the charger base 27 of the miniature centrifuge 25. This permits recharging of the nickel-cadmium batteries located inside the centrifuge 25. A miniature reading chart 39 is provided for determining blood hematocrits after centrifuging microhematocrit tubes in the miniature centrifuge 25. This centrifuge 25 enables rapid (30 seconds) determinations of blood hematocrit and rapid preparation of plasma from whole blood. It contains its own concentrically arranged battery supply 27 and can be operated for extended periods detached from the charger base 27. A plastic foam block 41 is positioned in the case 13 for containing reservoirs 43 in which standard solutions and samples are placed. The reservoirs 43 are mounted at a 45 angle so that the total contained volume can be efficiently aspirated into the Tygon sample inlet tubes 45. The reservoirs 43 are kept stoppered until immediately prior to inserting the Tygon sample inlet tubes 45 in order to minimize untoward gas exchange and/or contamination.

A container 47 is positioned in one corner of the case 13 for housing syringes, disposable hypodermic needles, lancets, tourniquets, alcohol, gauze sponges, capillary tubes with ammonium heparinate anticoagulant, plastic reservoirs, disposable 25p. l. pipet and bottles of standard solutions 49 which contain alcohol, pH standard, and sodium, potassium, and chloride standard. The commercially available pipet 51 shown sheathed is used for drawing 25p. 1. of plasma from the centrifuged capillary tube and diluting the plasma 1:12 in the plastic reservoirs 53 which contain a premeasured volume of buffer-diluent. The reservoir 55 has a disposable pipet 51 attached.

A timer scale 57, by the use of appropriate color coding, indicates the exact sequence of operations to follow in order to measure blood pH and plasma sodium, potassium and chloride. In practice, the operator turns the pointer knob 59, which controls a -minute timer mechanism, completely clockwise. As the pointer proceeds through its S-minute cycle, the operator simply performs the operations indicated at the precise point in time shown on the timer scale 57. All color coded instructions on the timer scale 57 are directly related to color coded control labels on the panel face. A toggle switch 61 operates to energize the heater circuits used to hold the electrode assembly at 37 C.

An ion selector knob 63 operates a switch containing four wafers and is constructed to minimize losses in high-impedance circuits. The ion selector knob 63 has four positions and as it is turned, it connects each individual electrode with the appropriate calibration and scale expansion circuitry, The labeling is color coded to match the timer scale 57. A toggle switch 65 operates to energize the meter reference and amplifier circuits. A pH control knob 67, appropriately color coded, operates a commercially available lO-tum potentiometer which is placed in the circuit through the ion selector switch 63 and permits precise standardization of the meter pH scale. The panel is provided with spare control knob 69 in the panel where future auxiliary control, if desired, can be installed. The chloride control knob 71, sodium control knob 73, and potassium control knob 75 are appropriately color coded and operate commercially available lO-turn precision potentiometers which are placed into the circuit through the ion selector switch 63 and permit precise standardization of their respective meter scales. A potassium scale control knob 77 connects to a gear train which controls the movement of a stainless steel shaft to which is connected a flat graduated scale. This scale permits direct readout of potassium concentration even though the electrode in use is responsive to both sodium and potassium ions.

A direct readout meter 79 positioned on the panel is commercially available and calibrated to permit direct readout of pH and millequivalents chloride, sodium and potassium per liter. An arbitrary logging scale is also included to permit assay of any electrotype containing fluid. A mirror surface 81 is provided in the center of the scale to preclude reading error due to parallax. The meter 79 includes a meter pointer 83 and a movable scale 85 calibrated in millequivalents potassium per liter. The case 13 is provided with the handle 87 with which to carry the entire analytical system. A temperature indicator 89 gives a visual indication of the temperature of the electrode chamber. An auxiliary input 91 is positioned in the center portion of the system panel.

In FIG. 2, which is a functional diagram of the system, the flow control syringe assembly 93 is shown in position for aspirating fluid, either standard solutions or samples, through the electrode assemblies 95 by clockwise movement of the load control knob 29 (FIG. 1). When the flow valve 33 is turned 90", shown functionally at 97 in FIG. 2, the contents of the syringes 101 can be discharged into the waste container 103. A highly stable reference junction 105 is maintained through a palladium-glass annulus and a hydrostatically pressurized bridge of 3.5 N potassium chloride. The 3.5 N potassium chloride does not precipitate at normal ambient temperatures but is sufficiently concentrated to insure stable conductivity. The tip of a commercially available silver-silver chloride electrode is immersed into the 3.5 N potassium chloride in a reservoir so that the level of the potassium chloride is approximately 8 inches above the annular junction. The reference electrode 105 feeds into the four-channel calibration circuit 107 which is switched by the four-position ion selector switch 63 (FIG. 1). The output of the calibration circuit feeds into the solid-state amplifier 109. The four specific ion electrodes feed into the high-impedance switch circuit and are individually switched into the photodiode chopper circuit 111. The output of the chopper 111 is fed into a high-impedance field effect transistor preamplifier 113. The output signal from the preamplifier is then further amplified and prepared for readout. Since each individual electrode has its own peculiarities, individual scale expansion potentiometers are provided for each channel. These are switched into the circuit by the ion selector switch. Individual scale expansion controls permit tailoring the output signal to the preprinted direct readout scale for any electrode of the appropriate specificity which might be inserted at some future time. The temperature of the aluminum heat block is controlled through the strategic placement of thermistor controlling elements and resistor heating elements. Temperature is indicated by additional thermistor sensors. Energy for heating the resistors is supplied from a built-in bank of nickel-cadmium cells which are kept charged by a built-in battery charger capable of operating from either 60 Hz. or 400 Hz. This feature enables battery charging either on the ground or on board aircraft. The battery charger also provides current for charging the nickel-cadmium cells 27 mounted within the miniature centrifuge 25.

In FIG. 3, which is an outline diagram of a rear view of the panel assembly showing the various electronic and fluid flow components. An expanded scale electrometer 121 is characterized by solid-state circuitry throughout. The scale expansion precision potentiometers 123 are used to set the span for the individual electrodes. A photodiode chopper 125 is mounted in the circuit between the high-impedance ion selector switch and the field effect transistor preamplifier 127 which amplifies the high-impedance AC signal from the photodiode chopper 125 and feeds it to the solid-state amplifier, scale expansion and readout circuitry. Four calibration potentiometers 129 serve to calibrate the pH, potassium, sodium and chloride channels. The appropriate potentiometer is switched into the circuit by means of the ion selector switch.

The meter switch 131, heater switch 133, ion selector switch 135, timer mechanism 137 and mercury battery 139 in the reference circuit are shown positioned in the panel beneath the meter 121. An lmplex panel 141 supports the miniature coaxial convectors 143 which accommodate mating connectors on the electrode cables. The inlet tubes 145 and 147 carry the fluids in the system to the electrode assembly. The two section flow valve 149 is constructed of Implex and is connected through the tubing 151 to the waste container 153. The plastic tubing 155 connects the flow valve 149 to the syringe assembly. The waste container receives waste from the syringes following the determination of pH, sodium, potassium and chloride.

Slots 157 are provided in the aluminum heat block 159 to accommodate thermistor sensing and controlling elements and heating resistors. An aluminum housing 161 lined with an insulating foam 163 accommodates the aluminum heat block 159. The terminal blocks 165 and 167 permit interconnection of the electronic circuitry 169 and 171 which includes the battery recharger and temperature controller. The specific ion electrodes 173 are positioned in the aluminum block 159. The reference electrode 105 inserts into the reservoir 175 and the reservoir connects to the rubber tubing 177 through bifurcation 179. The rubber tubing 177 is filled with 3.5 N potassium chloride which serves as a conductive hydrostatically pressurized bridge for this purpose.

The gear driven syringe assembly 93 includes the shaft 181 and operates to fill and empty the system. The rapid heat switch 183 and the temperature indicating meter 185 are located in the area of the reference electrode 105 which is held in position by the clamp 187. The cable 189 leads from the reference electrode 105 to the electronic circuitry.

ln FIGS. 4 and 5 there is shown a second version of the electrode assembly. In practice, this assembly 191, like the previously described one, is encased in a machined aluminum block for the measurement of pH. This assembly 191 features glass capillary electrodes 193 and 195 fabricated of potassium and sodium selective glass, respectively. The arrangement shown eliminates difficulties due to the entrapment of air bubbles. The sample is aspirated through the entire assembly, thus providing electrical continuity between all glass and silver electrodes and the reference junction at the dialysis membrane 197. Proceeding from left to right (FIG. 4) the sample is drawn through the stainless steel tube 199 to which is attached a plastic inlet tube (not shown). The sample flows through a capillary 193 compound of commercially available potassium selective glass which is surrounded by an external electrolyte of 0.1 N potassium chloride in which is inserted a silver-silver chloride wire 201. The sample flows through a capillary of sodium selective glass 195 which is surrounded by an internal electrolyte of 0.1 N sodium chloride in which is inserted a silver-silver chloride wire 203. The sample flows through a capillary drilled through an lmplex cylinder 205 along the top of which is inserted a commercially available permanent silver chloride wire electrode 207. The sample flows into a capillary 197 formed as shown in the exploded view (P16. 5) which underlies a cellophane membrane 209, a neoprene gasket 211 and a cylindrical port 213 through which 3.5 N potassium chloride establishes continuity between a silver-silver chloride reference electrode and the porous dialysis membrane 209. The sample flows through the flow valve (not shown) into the load syringes 93. The reference junction formed through the dialysis membrane 209 is particularly stable and reliable and requires minimum hydrostatic head. The permanent silver chloride wire electrode 207 used in the third section of the assembly 191 permits long term reliable measurement of chloride ions with no need for periodic replating with silver chloride.

Although the invention has been illustrated in the accompanying drawings and described in the foregoing specification in terms of preferred embodiments thereof, the invention is not limited to these embodrments or to the partrcular configurations mentioned. It will be apparent to those skilled in the art that our invention is readily adaptable for use in assaying any fluid if appropriate standards are used. Under optimum conditions, all determinations, including hematocrit, pl-l, sodium, potassium, and chloride, can be accomplished within 7 minutes after the blood is drawn.

Also, it should be understood that various changes, alterations, modifications and substitutions with respect to the construction details can be made in the arrangement of the several elements without departing from the true spirit and scope of the appended claims.

Having thus described our invention, what we claim as new and desire to secure by Letters Patent of the United States is:

1. A portable fluid analyzing system for making hematocrit, pH and electrolyte assaying determinations, comprising, in combination, a carrying case for containing the analyzing equipment, centrifuge means disposed in said case for measuring whole blood hematocrit and preparing plasma for electrolyte assay, an electrode first and second located in said case, a plurality of individual electrodes positioned in said electrode chambers, each of said electrodes having its own calibration potentiometer, fluid line means connected at one end thereof to said electrode chambers for delivering fluid from fluid test samples disposed at the other end of said fluid line means, first and second gear driven syringes, additional fluid line means connecting each of said syringes to a respective one of said electrode chambers for filling said electrode chambers with test fluid, load control means operatively attached to said gear driven syringes for driving said syringes, meter means for directly reading the various components in the fluid, switch means for selectively connecting said electrodes and calibration potentiometers to said meter means, a two-section valve in said additional fluid line means between said electrode chambers and said syringes for directing the fluid flow to a waste container and emptying said syringes after the fluid test operation, and means for maintaining the fluid in said chambers to be analyzed at a constant temperature so that results closely approach in vivo readings.

2. The portable fluid analyzing system defined in claim 1 wherein said electrode chambers are fabricated of glass and are positioned in an aluminum block which is maintained at a predetermined constant temperature thereby bringing the fluid in the electrode chamber to the proper operating tem- 

2. The portable fluid analyzing system defined in claim 1 wherein said electrode chambers are fabricated of glass and are positioned in an aluminum block which is maintained at a predetermined constant temperature thereby bringing the fluid in the electrode chamber to the proper operating temperature for analysis.
 3. The portable fluid analyzing system defined in claim 2 wherein said electrode chambers includes a heat control circuit, said heat control circuit being thermistor controlled and transistor regulated.
 4. The portable fluid analyzing system defined in claim 3 wherein said meter means for directly reading the various components in the fluid includes a high-impedance solid-state electrometer having a precalibrated direct readout scale. 